Predicting the Recurrence of Gastric Cancer Using the Textural Features of Perigastric Adipose Tissue on [18F]FDG PET/CT.

This study aimed to assess the relationship between the histopathological and textural features of perigastric adipose tissue (AT) on 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) and to evaluate the prognostic significance of perigastric AT textural features in predicting recurrence-free survival (RFS) in patients with gastric cancer. Sixty-nine patients with gastric cancer who underwent staging [18F]FDG PET/CT and subsequent curative surgery were retrospectively reviewed. Textural features of perigastric AT were extracted from PET images. On histopathological analysis, CD4, CD8, and CD163 cell infiltration and matrix metalloproteinase-11 and interleukin-6 (IL-6) expression in perigastric AT were graded. The degree of CD163 cell infiltration in perigastric AT was significantly correlated with the mean standardized uptake value (SUV), SUV histogram entropy, grey-level co-occurrence matrix (GLCM) energy, and GLCM entropy of perigastric AT. The degree of IL-6 expression in the perigastric AT was significantly correlated with the mean and median SUVs of perigastric AT. In multivariate survival analysis, GLCM entropy, GLCM dissimilarity, and GLCM homogeneity of perigastric AT were significant predictors of RFS. The textural features of perigastric AT on [18F]FDG PET/CT significantly correlated with inflammatory response in perigastric AT and were significant prognostic factors for predicting RFS in patients with gastric cancer.

Low LATS2 expression is associated with poor prognosis in non-small cell lung carcinoma.

Large tumor suppressor kinase 2 (LATS2) is a core component in the Hippo signaling pathway, and it functions as a tumor suppressor associated with tumor cell proliferation and apoptosis. The purpose of this study is to explore LATS2 expression and its clinicopathological significance in non-small cell lung cancer (NSCLC). We examined LATS2 protein expression by immunohistochemistry in 184 resected NSCLC specimens using tissue microarrays. Low LATS2 expression was significantly related to disease recurrence (p = 0.047). In survival analysis, the low LATS2 expression group showed a statistically poorer overall survival (OS) (p = 0.004) and disease-free survival (DFS) (p = 0.014) than the high expression group. In multivariate analysis, downregulated LATS2 expression in NSCLC could be an independent prognostic factor of poor OS and DFS. Furthermore, we evaluated the prognostic significance of LATS2 expression in two major NSCLC subtypes, squamous cell carcinoma and adenocarcinoma. The low LATS2 expression group showed worse prognosis than the high LATS2 expression group (OS [p = 0.144] and DFS [p = 0.022] in squamous cell carcinoma and OS [p = 0.045] and DFS [p = 0.271] in adenocarcinoma). We demonstrated that downregulated LATS2 expression may predict aggressive biologic behavior and a worse prognosis in NSCLC and we also suggested the possibility of LATS2 as a therapeutic target in both squamous cell carcinoma and adenocarcinoma.

Diagnostic and therapeutic approach for acute paraquat intoxication.

Paraquat (PQ) has known negative human health effects, but continues to be commonly used worldwide as a herbicide. Our clinical data shows that the main prognostic factor is the time required to achieve a negative urine dithionite test. Patient survival is a 100% when the area affected by ground glass opacity is <20% of the total lung volume on high-resolution computed tomography imaging 7 days post-PQ ingestion. The incidence of acute kidney injury is approximately 50%. The average serum creatinine level reaches its peak around 5 days post-ingestion, and usually normalizes within 3 weeks. We obtain two connecting lines from the highest PQ level for the survivors and the lowest PQ level among the non-survivors at a given time. Patients with a PQ level between these two lines are considered treatable. The following treatment modalities are recommended to preserve kidney function: 1) extracorporeal elimination, 2) intravenous antioxidant administration, 3) diuresis with a fluid, and 4) cytotoxic drugs. In conclusion, this review provides a general overview on the diagnostic procedure and treatment modality of acute PQ intoxication, while focusing on our clinical experience.

Complicated calcified alloplastic implants in the nasal dorsum: A clinical analysis.

BACKGROUND: In rhinoplasty, calcification around silicone implants is frequently observed in the tip dorsum (TD) area. Additionally, based on a review of various literature, it is presumed that calcification in silicone implants occurs due to both inflammatory chemical reactions and physical friction against the tissue. The calcification of nasal silicone implants not only results in the functional loss of the implants, but also leads to material deformation. However, there is a lack of research on calcification of nasal silicone implants in the current literature. AIM: To elucidate various clinical characteristics of calcification around nasal silicone implants, using histological and radiological analysis. METHODS: This study analyzed data from 16 patients of calcified nasal implants, who underwent revision rhinoplasty for various reasons after undergoing augmentation rhinoplasty with silicone implants. The collected data included information on implant duration, implant types, location of calcification, presence of inflammatory reactions, and computed tomography (CT) scans. RESULTS: The most common location of calcification, as visually analyzed, was in the TD area, accounting for 56%. Additionally, the analysis of CT scans revealed a trend of increasing Hounsfield Unit values for calcification with the duration of implantation, although this trend was not statistically significant (P = 0.139). CONCLUSION: Our study shows that reducing the frequency of calcification may be achievable by using softer silicone implants and by minimizing the damage to perioperative tissues.

Clinicopathological Significance of DUB3 Expression in Non-small Cell Lung Cancer and Relationship Between DUB3 Expression and LATS1 Expression.

BACKGROUND/AIM: Deubiquitinating enzyme 3 (DUB3) is a member of the ubiquitin-specific proteases family involved in regulating cell proliferation, invasion, and apoptosis. However, the biological role and clinicopathological significance of DUB3 expression have not been elucidated in non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: We evaluated the expression of DUB3 by immunohistochemistry using tissue microarrays and assessed the clinicopathologic significance of DUB3 expression levels in 187 patients with NSCLC, including its two major subtypes (93 cases of adenocarcinoma and 72 cases of squamous cell carcinoma). RESULTS: In adenocarcinoma, we observed that DUB3 expression had an effect on tumor size (p=0.030), vessel invasion (p=0.038), T stage (p=0.014), and tumor recurrence (p=0.002). Kaplan-Meier curves with log-rank test showed that high DUB3 expression was correlated with significantly more favorable clinical outcomes compared to those of the low expression group in adenocarcinoma (p=0.013). Multivariate analysis of disease-free survival also demonstrated that DUB3 expression is an independent prognostic factor in lung adenocarcinoma (p=0.017). Additionally, we identified the correlation between DUB3 and the expression of large tumor suppressor kinase 1 expression, a core protein of the Hippo pathway. CONCLUSION: DUB3 could function as a tumor suppressor by regulating the Hippo pathway in lung adenocarcinoma and can be considered a powerful predictive factor and therapeutic target.

Relationship of FDG Uptake of the Reticuloendothelial System with Tumor Immune Microenvironment and Prognosis in Patients with Gastric Cancer.

2-deoxy-2-[18F]fluoro-D-glucose (FDG) uptake of the reticuloendothelial system, including the bone marrow (BM) and spleen, on positron emission tomography/computed tomography (PET/CT) has been shown to be a significant prognostic factor in diverse malignancies. However, the relationship between FDG uptake of the BM and spleen and histopathological findings, including the tumor immune microenvironment, has not been fully evaluated. This study aimed to investigate the relationship of FDG uptake in the BM and spleen with histopathological findings and recurrence-free survival (RFS) in patients with gastric cancer. Seventy patients with gastric cancer who underwent pre-operative FDG PET/CT and subsequent curative surgery were retrospectively enrolled. On image analysis, the BM-to-liver uptake ratio (BLR) and spleen-to-liver uptake ratio (SLR) were measured from PET/CT images, and on immunohistochemical analysis, the densities of immune cell infiltration in the tumor tissue were graded. The BLR and SLR showed significant positive correlations with the grades of CD163 cell and CD8 cell infiltration in the tumor tissue, respectively (p < 0.05). In multivariate survival analysis, both BLR and SLR were significant predictors of RFS (p < 0.05). FDG uptake in the BM and spleen might be potential imaging biomarkers for evaluating tumor immune microenvironment conditions and predicting RFS in patients with gastric cancer.

Automated Diagnosis of Cervical Intraepithelial Neoplasia in Histology Images via Deep Learning.

Artificial intelligence has enabled the automated diagnosis of several cancer types. We aimed to develop and validate deep learning models that automatically classify cervical intraepithelial neoplasia (CIN) based on histological images. Microscopic images of CIN3, CIN2, CIN1, and non-neoplasm were obtained. The performances of two pre-trained convolutional neural network (CNN) models adopting DenseNet-161 and EfficientNet-B7 architectures were evaluated and compared with those of pathologists. The dataset comprised 1106 images from 588 patients; images of 10% of patients were included in the test dataset. The mean accuracies for the four-class classification were 88.5% (95% confidence interval [CI], 86.3-90.6%) by DenseNet-161 and 89.5% (95% CI, 83.3-95.7%) by EfficientNet-B7, which were similar to human performance (93.2% and 89.7%). The mean per-class area under the receiver operating characteristic curve values by EfficientNet-B7 were 0.996, 0.990, 0.971, and 0.956 in the non-neoplasm, CIN3, CIN1, and CIN2 groups, respectively. The class activation map detected the diagnostic area for CIN lesions. In the three-class classification of CIN2 and CIN3 as one group, the mean accuracies of DenseNet-161 and EfficientNet-B7 increased to 91.4% (95% CI, 88.8-94.0%), and 92.6% (95% CI, 90.4-94.9%), respectively. CNN-based deep learning is a promising tool for diagnosing CIN lesions on digital histological images.

Relationship of FDG PET/CT Textural Features with the Tumor Microenvironment and Recurrence Risks in Patients with Advanced Gastric Cancers.

The relationship between 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) textural features and histopathological findings in gastric cancer has not been fully evaluated. We investigated the relationship between the textural features of primary tumors on FDG PET/CT with histopathological findings and recurrence-free survival (RFS) in patients with advanced gastric cancer (AGC). Fifty-six patients with AGC who underwent FDG PET/CT for staging work-ups were retrospectively enrolled. Conventional parameters and the first- and second-order textural features of AGC were extracted using PET textural analysis. Upon histopathological analysis, along with histopathological classification and staging, the degree of CD4, CD8, and CD163 cell infiltrations and expressions of interleukin-6 and matrix-metalloproteinase-11 (MMP-11) in the primary tumor were assessed. The histopathological classification, Lauren classification, lymph node metastasis, CD8 T lymphocyte and CD163 macrophage infiltrations, and MMP-11 expression were significantly associated with the textural features of AGC. The multivariate survival analysis showed that increased FDG uptake and intra-tumoral metabolic heterogeneity were significantly associated with an increased risk of recurrence after curative surgery. Textural features of AGC on FDG PET/CT showed significant correlations with the inflammatory response in the tumor microenvironment and histopathological features of AGC, and they showed significant prognostic values for predicting RFS.

A novel role of CRTC2 in promoting nonalcoholic fatty liver disease.

OBJECTIVE: Diet-induced obesity is often associated with nonalcoholic fatty liver disease (NAFLD), which instigates severe metabolic disorders, including cirrhosis, hepatocellular carcinoma, and type 2 diabetes. We have shown that hepatic depletion of CREB regulated transcription co-activator (CRTC) 2 protects mice from the progression of diet-induced fatty liver phenotype, although the exact mechanism by which CRTC2 modulates this process is elusive to date. Here, we investigated the role of hepatic CRTC2 in the instigation of NAFLD in mammals. METHODS: Crtc2 liver-specific knockout (Crtc2 LKO) mice and Crtc2 flox/flox (Crtc2 f/f) mice were fed a high fat diet (HFD) for 7-8 weeks. Body weight, liver weight, hepatic lipid contents, and plasma triacylglycerol (TG) levels were determined. Western blot analysis was performed to determine Sirtuin (SIRT) 1, tuberous sclerosis complex (TSC) 2, and mammalian target of rapamycin complex (mTORC) 1 activity in the liver. Effects of Crtc2 depletion on lipogenesis was determined by measuring lipogenic gene expression (western blot analysis and qRT-PCR) in the liver as well as Oil red O staining in hepatocytes. Effects of miR-34a on mTORC1 activity and hepatic lipid accumulation was assessed by AAV-miR-34a virus in mice and Ad-miR-34a virus and Ad-anti-miR-34a virus in hepatocytes. Autophagic flux was assessed by western blot analysis after leupeptin injection in mice and bafilomycin treatment in hepatocytes. Lipophagy was assessed by transmission electron microscopy and confocal microscopy. Expression of CRTC2 and p-S6K1 in livers of human NAFLD patients was assessed by immunohistochemistry. RESULTS: We found that expression of CRTC2 in the liver is highly induced upon HFD-feeding in mice. Hepatic depletion of Crtc2 ameliorated HFD-induced fatty liver disease phenotypes, with a pronounced inhibition of the mTORC1 pathway in the liver. Mechanistically, we found that expression of TSC2, a potent mTORC1 inhibitor, was enhanced in Crtc2 LKO mice due to the decreased expression of miR-34a and the subsequent increase in SIRT1-mediated deacetylation processes. We showed that ectopic expression of miR-34a led to the induction of mTORC1 pathway, leading to the hepatic lipid accumulation in part by limiting lipophagy and enhanced lipogenesis. Finally, we found a strong association of CRTC2, miR-34a and mTORC1 activity in the NAFLD patients in humans, demonstrating a conservation of signaling pathways among species. CONCLUSIONS: These data collectively suggest that diet-induced activation of CRTC2 instigates the progression of NAFLD by activating miR-34a-mediated lipid accumulation in the liver via the simultaneous induction of lipogenesis and inhibition of lipid catabolism. Therapeutic approach to specifically inhibit CRTC2 activity in the liver could be beneficial in combating NAFLD in the future.

Constitutive overexpression of Id-1 in mammary glands of transgenic mice results in precocious and increased formation of terminal end buds, enhanced alveologenesis, delayed involution.

Inhibitor of differentiation-1 (Id-1) has been shown to play an essential role in cell proliferation, invasion, migration, and anti-apoptosis. However, the effect of Id-1 in mammary gland development remains unknown. Here, we generated MMTV-Id-1 transgenic mice to study the role of Id-1 in mammary gland development. In virgin mice, Id-1 overexpression led to precocious development and delayed regression of terminal end buds (TEBs) compared with wild-type mice. The number of BrdU-positive cells and the expression of Wnt signaling molecules, ß-catenin and cyclin D1, which regulate ductal extension and TEB formation in virgin, were statistically higher in Id-1 transgenic mice than in wild-type mice. Id-1 also had an effect on the formation and proliferation of lobuloalveolar structures during early and mid-pregnancy. Id-1 transgenic mice had more lobulated and prominent alveolar budding than wild-type mice and had significantly greater counts of lobuloalveolar structures in early pregnancy. The expression of BrdU, ß-catenin, and cyclin D1 was also predominantly increased in Id-1 transgenic mice. Moreover, Id-1 transgenic mice showed delayed involution. Id-1 regulated the expression levels of anti-apoptotic Bcl-2 and pro-apoptotic Bax, and resulted in delay of apoptotic peak during postlactational involution. We also found that Id-1 was able to modulate expression of the regulators of Wnt/ß-catenin signaling such as phospho-Akt, BMP2, FGF3, and RAR-ß in tubuloalveolar development of mammary glands. Taken together, our results suggest that Id-1 plays a pivotal role in mammary gland development through Wnt signaling-mediated acceleration of precocity and alveologenesis and Bcl-2 family members-mediated delay of involution.

The use of pluripotent stem cell for personalized cell therapies against neurological disorders.

Although there are a number of weaknesses for clinical use, pluripotent stem cells are valuable sources for patient-specific cell therapies against various diseases. Backed-up by a huge number of basic researches, neuronal differentiation mechanism is well established and pluripotent stem cell therapies against neurological disorders are getting closer to clinical application. However, there are increasing needs for standardization of the sourcing pluripotent stem cells by establishing stem cell registries and banking. Global harmonization will accelerate practical use of personalized therapies using pluripotent stem cells.

Smad4 may help to identify a subset of colorectal cancer patients with early recurrence after curative therapy.

BACKGROUND/AIMS: Loss of Smad4 function is associated with the acquisition of advanced colorectal cancer phenotypes. We investigated the role of Smad4 as a prognostic marker after curative therapy. METHODOLOGY: Four hundred and twenty nine consecutive colorectal cancers were analyzed by tissue microarray-based immunohistochemical assay. RESULTS: Smad4 protein was expressed in 61.5% (24/39), 53.1% (77/145), 41.3% (78/189) and 34.8% (16/46) of stage I, II, III and IV cancers, respectively. Lymphovascular invasion and lymph node metastasis were strongly correlated with the loss of Smad4 expression (p<0.0001 and p=0.002, respectively). Disease-free survival did not differ between Smad4-positive and Smad4-negative cancers. In stage III disease, time to recurrence after curative therapy was shorter in the Smad4-negative than in the Smad4- positive cancers (20.1±15.1 vs. 34.6 ± 34.1 months, p=0.035). CONCLUSIONS: Smad4 protein is of no value in predicting recurrence after curative therapy in colorectal cancer, but it may be helpful in identifying a subset of patients with early recurrence after curative therapy.

Clinical features and literature review related to the material differences in thread rhinoplasty: Two case reports.

BACKGROUND: Thread rhinoplasty can trigger a reaction to thread material, which is a foreign body. We compared clinical features induced by absorbable and non-absorbable threads following thread rhinoplasty. CASE SUMMARY: Two patients who underwent different thread materials showed different clinical courses and different Hounsfield unit (HU) values in computed tomography. Patients with absorbable thread showed high HU values similar to a metallic material, and the HU value of inflammation was similar to vascular tissues with a lot of water (250). In the intraoperative field, absorbable thread materials and micro-abscesses were observed. In contrast, in the case of a non-absorbable thread, an object presumed to be thread was seen on the computed tomography (CT), and the HU value of inflammatory tissues was less than 100. In both patients, post-operative HU decreased to less than 100 and the clinical course improved. In both cases, histopathologic findings revealed foreign body granuloma associated with inflammation. CONCLUSION: Absorbable threads were more aggressive and are more easily detected on CT.

Prognostic significance of imaging features of peritumoral adipose tissue in FDG PET/CT of patients with colorectal cancer.

PURPOSE: This study investigated the relationship of imaging features of primary tumor and peritumoral VAT on PET/CT with histopathological findings of peritumoral VAT and recurrence-free survival (RFS) in patients with colorectal cancer. METHODS: We retrospectively reviewed 133 patients diagnosed with colorectal cancer who underwent staging FDG PET/CT and received curative surgery. Histogram-based imaging features of primary tumor and peritumoral VAT were extracted from PET/CT images. Based on histopathological analysis of peritumoral VAT, the degree of CD4, CD8, and CD163 cell infiltration and the expression of matrix metalloproteinase-11 and interleukin 6 (IL-6) were graded. Differences in imaging parameters based on the histopathological results and the relationships between imaging features and RFS were assessed. RESULTS: Mean CT-attenuation and SUV of peritumoral VAT showed significant positive correlation with CD163 cell infiltration and IL-6 expression of peritumoral VAT. Univariable survival analysis revealed significant correlation between RFS and the mean CT-attenuation, mean SUV, and first-order SUV entropy of peritumoral VAT (p < 0.05). Multivariable analysis indicated that mean SUV and SUV entropy of peritumoral VAT remained significant predictors of RFS after adjustment for age, sex, and T stage (p < 0.05). CONCLUSION: FDG uptake of peritumoral VAT was significantly associated with inflammatory response in peritumoral VAT and was an independent predictor of RFS in colorectal cancer patients.

A Huge Plantar Intramuscular Hemangioma in the Plantar Area Treated Surgically: A Case Report and Literature Review.

Intramuscular hemangioma (IH) is rare, accounting for only 0.8% of all hemangioma cases. In particular, IH of the foot has only been reported a few times. In such cases, the symptoms typically include tenderness and swelling, often in relation to physical activity, but tingling or impaired function may also be present. Here, we report a patient who presented with a significant IH in the plantar area treated surgically. A 25-year-old female visited our hospital with pain in the plantar aspect of the right foot. She had noticed a mass about 10 years prior. She had previously experienced pain only when pressing the mass, but the pain subsequently became more regular pain and was exacerbated by exercise. In fact, the pain became so intense that she could not sleep well. Upon physical examination, mild swelling and tenderness of the plantar area were noted in the second to the fourth metatarsal. Sensation and motor reflexes were normal and the results of Tinel's test were negative. Plain radiographs of the right foot revealed phleboliths scattered throughout the first to third intermetatarsal spaces. Magnetic resonance imaging revealed a space-occupying multilobulated mass (5.6 × 2.8 × 2.5 cm) located in the flexor digitorum brevis (FDB) muscle, which penetrated the plantar fascia and spread to the subcutaneous layer. In T2-weighted images, the lesion displayed a hyperintense signal compared to the surrounding skeletal muscle. Based on radiological findings, we suspected IH. The mass surrounded by the FDB muscle was exposed and completely removed via wide excision. IH consisting of cavernous-like vascular structures was diagnosed on pathology. At 1-year follow-up, the patient was almost asymptomatic and had recovered almost full range of motion in the plantar area. Histological analysis and surgery are recommended to remove intramuscular hemangiomas in the plantar area, but if the patient is not suitable for surgery, sclerotherapy or combination treatment should also be considered.

Clinicopathological significance of nuclear PTEN expression in colorectal adenocarcinoma.

AIMS: Tumour suppressor phosphatase and tensin homologue (PTEN) is an important negative regulator for the PIP3/Akt signalling pathway that promotes cell proliferation and inhibits apoptosis. Inactivation of PTEN by mutation, deletion and promoter hypermethylation has been demonstrated in a range of cancers. The aim was to investigate whether the loss of nuclear PTEN protein expression correlates with conventional clinicopathological parameters and patient survival. METHODS AND RESULTS: Immunohistochemistry staining for PTEN was performed on a tissue microarray of 19 samples of normal colonic mucosa, 14 adenomatous polyps, 482 adenocarcinomas and 56 metastatic lymph nodes. All 19 normal colonic mucosa samples (100%) were positive and 12 (85.7%) out of 14 adenomatous polyps were positive for PTEN. However, only 241 (50.0%) of the 482 colorectal adenocarcinomas and 26 (46.4%) of the 56 metastatic lymph nodes were positive for PTEN. Loss of PTEN expression was related to defective mismatch repair protein expression and colonic localization rather than rectal localization. On univariate survival analysis, patients with PTEN- adenocarcinoma revealed a poor overall and disease-free survival (P = 0.030 and P = 0.046, respectively). On multivariate analysis, a significant difference was observed in patients with stage II cancer that was not observed in other stages. CONCLUSIONS: Nuclear PTEN expression gradually decrease during the normal-adenoma-adenocarcinoma-metastasis sequence, which suggests an important role for PTEN in carcinogenesis. Moreover, loss of nuclear PTEN expression was a marker of poor clinical outcome in patients with stage II colorectal cancer.

Loss of ARID1A expression is associated with poor prognosis in non-small cell lung cancer.

Adenine-thymine-rich inactive domain-containing protein 1A (ARID1A) is a large subunit of the switch-sucrose nonfermenting (SWI-SNF) complex. ARID1A is considered to be a tumor suppressor in various cancers. We investigated the clinicopathological significance including prognosis of ARID1A expression in non-small cell lung cancer (NSCLC). ARID1A expression was studied by tissue microarray immunohistochemical analysis of 171 surgically resected NSCLC specimens including adenocarcinoma (ADC) and squamous cell carcinoma (SCC) on tissue microarray. Semiquantitative immunohistochemical score was obtained by multiplying the intensity and percentage scores. The overall score was further simplified by dichotomizing into either negative (score < 4) or positive (score ≥ 4) for each patient. The ARID1A-negative group revealed significantly higher correlations with male sex (p = 0.020), larger tumor size (p = 0.007), SCC than with ADC (p = 0.023) and smoking (p = 0.001). Univariate survival analysis showed that the ARID1A-negative group had a significantly shorter cancer specific survival than the ARID1A-positive group (p = 0.018). Multivariate survival analysis showed that ARID1A negativity (p = 0.022) were independent prognostic factors related with shorter cancer specific survival for NSCLC. In conclusion, Loss of ARID1A expression is a potential molecular marker to predictive of poor prognosis of NSCLC.

Clinicopathological correlation of PD-L1 and TET1 expression with tumor-infiltrating lymphocytes in non-small cell lung cancer.

The immunohistochemical analysis of PD-L1 expression is still important in cancer immunotherapy. PD-L1 expression is affected by various tumor microenvironmental factors including tumor infiltrating lymphocytes (TILs) and DNA methylation biomarkers. Given the complex communication between tumor cells and immune cells, we analyzed the expression of PD-L1 and TET1 with TILs in human NSCLC and the correlation with various clinicopathological characteristics and patient prognosis. A total of 96 cases of NSCLC were enrolled in this study. Using tissue microarray, we performed immunohistochemical staining to analyze PD-L1 and TET1 expression. Image-Pro Plus was used as an automated imaging analysis software program to analyze the density of CD3+, CD4+ and CD8 + TILs. PD-L1 expression was positively correlated with the density of CD3+, CD4+ and CD8 + TILs (p = 0.038, p = 0.020, and p = 0.009, respectively); however, no significant relationship existed between TET1 expression and any TILs. The survival analysis revealed that a high PD-L1 expression was associated with favorable prognosis for OS (p = 0.049) and DFS (p = 0.029) in advanced-stage II-IV patients, but not in early stage I. Density of CD8+ TILs was an independent and favorable prognostic factor for DFS (p = 0.008) and OS (p = 0.002) in early-stage I patients. However, high TET-1 expression was associated with poor prognosis for OS (p = 0.029) in total NSCLC patients. These findings suggest the correlation and favorable prognostic impact of PD-L1 and TILs in NSCLC. In addition, DNA demethylase TET1 has oncogenic effects, showing association with poor prognosis.

Ovarian yolk sac tumor with epithelial tumor component in a postmenopausal woman - case report and literature review.

Ovarian yolk sac tumors are common germ cell tumors usually arising in young women. Yolk sac tumors in elderly women are infrequently encountered and most of them are combined with other epithelial tumor components including endometrioid carcinoma or serous carcinoma. Here, we report an extremely rare case of a yolk sac tumor with mucinous tumor and large cell neuroendocrine carcinoma components in a postmenopausal woman, which is the third yolk sac tumor case with a neuroendocrine tumor element in an elderly woman. An 82-year-old female visited our hospital due to abdominal distention. Abdominal computed tomography (CT) demonstrated a solid and cystic mass, measuring about 9.0 cm in the largest diameter. A total hysterectomy with bilateral salpingo-oophorectomy and excisional biopsy of the peritoneal metastatic lesions was performed. Histologic evaluation revealed a malignant ovarian tumor composed of a variety of tumor components, including a yolk sac tumor, a mucinous tumor with multifocal mucinous carcinomatous areas, and a large-cell neuroendocrine carcinoma. After surgery, the patient refused further treatment and the disease recurred in the pelvic peritoneum and a left supraclavicular lymph node nine months later.